Do we know what causes Merkel cell carcinoma?

Cancer is caused by changes in the DNA inside of cells. DNA is the chemical in each of our cells that makes up our genes – the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. But DNA affects more than just how we look.

Some genes help control when our cells grow, divide into new cells, and die. Genes that help cells grow, divide, and stay alive are called oncogenes. Genes that keep cell growth in check by slowing down cell division or causing cells to die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes. Changes in several different genes are usually needed for a cell to become cancerous.

Researchers don’t yet know all of the DNA changes that result in MCC, but they have found that many of these cancers have changes in tumor suppressor genes.

MCC does not seem to run in families, so the DNA changes that lead to MCC are not likely to be inherited from a person’s parents. Instead, these changes probably take place during a person’s lifetime. Sometimes these changes might just be random events that happen inside cells, without having an outside cause. But sometimes the cause might be something specific, like long-term sun exposure or infection with the Merkel cell polyomavirus (MCV).

Ultraviolet (UV) radiation can damage the DNA inside skin cells. Sometimes this damage affects certain genes that control how and when cells grow and divide, which may be the first step on the path to cancer.

The role of MCV infection in the development of MCC is not yet clear. For one thing, it’s not clear exactly how infection with MCV might lead to MCC. Researchers have found that the virus can cause cells to make a protein that turns off tumor suppressor genes, which might be how this happens.

The importance of MCV infection might help explain why the risk of MCC is higher in people with weakened immune systems. It might be that the virus is normally kept in check by the immune system. A suppressed immune system could allow the virus to grow and flourish, which in turn might raise the risk of MCC.

Scientists are looking for the specific DNA changes inside MCC cells to help explain what causes it. A better understanding of how damaged DNA leads to MCC might also be used to design treatments to overcome or repair the damage.